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08 Sep 2017

Shared insights with Chris Mok on HKU-Pasteur Research Pole’s efforts in H7N9 avian flu surveillance

The avian flu A(H7N9) has appeared in Mainland China since March 2013. Chinese health authorities have confirmed 1,584 cases of infections in humans so far, with a mortality rate coming close to 40%. The latest (fifth) epidemic wave that started in the winter of 2016-2017 caused dramatically more cases in humans compared to the previous waves. This flare-up of H7N9 infections raised serious concerns from the government and the public and highlighted the crucial need to maintain an intensive surveillance of this emerging virus. Since H7N9 has been identified, HKU-Pasteur Research Pole has focused on understanding the pathogenicity of the virus from multiple angles such as basic research, epidemiology and clinical investigation. This research effort aims at exploring how this avian virus has overcome the species barrier to infect humans. Recently, Malik Peiris, Chris Mok and their colleagues published two papers describing the clinical and epidemiological aspects of the H7N9 virus isolated from the fifth wave. Their findings can contribute to explain the sudden raise of human cases during the last season.

Treatment of a patient in Wuhan (Hubei), February 2017. © AFP

The fifth epidemic wave of the avian flu A(H7N9), which appeared in 2013 in Shanghai and Anhui province, has started in October 2016. It caused more human cases than the previous four waves and stretched for a longer period of time. With over 700 detected patients, the fifth wave represents almost the half of the total number of cases since the virus has emerged. Furthermore, governments and scientists know that there might be many mild or asymptomatic cases that have not been recognized and thus the actual numbers could be higher than the official record.

Different from the H5N1 virus (which mainly attacks healthy children and young adults), H7N9 mainly targeted the elderly population or patients with underlying diseases. However, similar to H5N1, human with H7N9 infection usually started up with upper respiratory symptoms: fever, cough, running nose etc. Many cases developed pneumonia, or even progressed to acute respiratory distress syndrome, septic shock and eventually died from multi-organ failure. The mortality rate in humans is high: 40% (60% for H5N1; 0,1% for seasonal flu viruses). Infections are associated with an exposure to infected live poultry or to contaminated environments (such as markets).

According to the Influenza Risk Assessment Tool (IRAT) of the US Centers for Disease Control and Prevention (CDC), H7N9 is the emerging virus with one of the highest potential risk for public health among Influenza A viruses, even though there is still no evidence of sustained human-to-human transmission to date.

The genetic changes in the virus can have important consequences on the control and surveillance strategies. Thus, HKU-Pasteur Research Pole is maintaining continuous research on H7N9 since it has emerged. The team of Malik Peiris (co-director) and Chris Mok (principal investigator) was one of the first group to characterize H7N9 pathogenicity and identify the viral determinants using a mouse model in 2013. They have kept pursuing a better understanding of the virus with serological, epidemiological and clinical studies. Recently, they found that the H7N9 virus circulating in the Guangdong province adjacent to the border of the Special Administrative Region of Hong Kong, has further adapted and evolved to a high-pathogenecity phenotype in poultry, similar to the H5N1 virus. In their study, a new genetic insertion in the hemagglutinin gene (the viral surface protein responsible for the binding of the virus to the membrane of host cells) was identified in the H7N9 virus. This adaptation makes the virus deadly to chickens and some other avian species (death within 24 hours after infection), and it was shown that such mutation in the H5N1 virus increases the virulence in mammalian hosts. In collaboration with the Guangdong CDC, HKU-PRP scientists found that 9 out of 60 human cases were actually infected by the new highly pathogenic avian influenza H7N9 (HPAI), while it had not been recognized during patients' hospitalization. They published their findings in two papers in July and August 2017 (in Eurosurveillance and Emerging Infectious Diseases) with a detailed clinical description of an infected patient and the epidemiological situation in Guangdong.

Dr Chris Mok in HKU-Pasteur Research Pole laboratories. © HKU-PRP

We are actively collaborating with the Chinese CDC and the First Affiliated Hospital of the Guangzhou Medical University with which we have a close partnership since 2014. We then have a privileged access to surveillance data and clinical samples in the Guangdong province, especially for H7N9 infections” Chris Mok said. “The information obtained through this network enabled us to describe the prevalence of H7N9 viruses in Guangdong poultry markets during the fifth wave, and to compare the epidemiological and basic clinical characteristics between patients infected with the low pathogenic and the highly pathogenic H7N9 viruses” he added.

Their research further showed that the duration of hospitalisation was longer in the patients infected with the mutated virus compared to the previous one. However, there is still a lack of strong evidence showing that the virus can transmit from human to human. Surprisingly, drug resistance was found in the case study patient as early as 2 days after the antiviral treatment.

By analysing the results of standardized questionnaires, we showed that the exposure to poultry markets is still a comparable risk factor for both HPAI and LPAI viruses, but we found touching sick or dead poultry as a more important risk factor for the mutated H7N9 infection, followed by raising backyard poultry. These results are important and must be taken into account for the control of future outbreaks, especially now that the latest cases of H7N9 infections are detected in more rural area of China where backyard poultry is more prevalent” Mok warned. “We still have a lot of questions on this newly identified virus as we don’t really know yet its impact on human and poultry. Rapid occurrence of drug resistance after the antiviral treatment is definitely our major concern. But we still need more data to come up with a conclusion” Chris Mok reported.

During summer, environmental conditions are not favourable for virus transmission to humans, so new cases are now detected sporadically, but what will happen during the next outbreak season in October-November? “There will probably be a competition between the two strains, but we cannot know yet if the highly pathogenic H7N9 virus will replace the low pathogenic virus or if they will coexist. Besides, H7N9 vaccine which targets the previous virus strain will be launched in China very soon, and it will cause a new source of uncertainty. It has to be considered, even if scientific points of view on that matter are divided. Vaccination prevents symptoms in birds, but cannot prevent the transmission and the circulation of the virus in animals, and so one doesn’t have a warning signal anymore by observing dead poultry when an outbreak occurs. Thus, an intense surveillance must be maintained” the researcher explained.

The two published articles:

Epidemiology of human infections with highly pathogenic avian influenza A(H7N9) virus in Guangdong, 2016 to 2017, Euro Surveill. 2017 Jul 6;22(27).
Kang M, Lau EHY, Guan W, Yang Y, Song T, Cowling BJ, Wu J, Peiris M, He J, Mok CKP

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China
, Emerg Infect Dis. 2017 Jul;23(8):1332-1340.
Ke C, Mok CKP, Zhu W, Zhou H, He J, Guan W, Wu J, Song W, Wang D, Liu J, Lin Q, Chu DKW, Yang L, Zhong N, Yang Z, Shu Y, Peiris JSM.

References:

Pathogenicity of the Novel A/H7N9 Influenza Virus in Mice (Mok et al., 2013)

Epidemiology of human infections with highly pathogenic avian influenza A(H7N9) virus in Guangdong, 2016 to 2017 (Kang et al., 2017) 

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China (Ke et al., 2017)

FAO, H7N9 situation update

WHO, Human infection with avian influenza A(H7N9) virus – China

European Centre for Disease Prevention and Control, Factsheet on A(H7N9)